Target Information
| Target General Information | Top | |||||
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| Target ID |
T88452
(Former ID: TTDS00068)
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| Target Name |
Corticosteroid-binding globulin (SERPINA6)
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| Synonyms |
Transcortin; SERPINA6; CBG
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| Gene Name |
SERPINA6
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| Target Type |
Successful target
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[1] | ||||
| Disease | [+] 3 Target-related Diseases | + | ||||
| 1 | Asthma [ICD-11: CA23] | |||||
| 2 | Postoperative inflammation [ICD-11: 1A00-CA43] | |||||
| 3 | Respiratory system disease [ICD-11: CB40-CB7Z] | |||||
| Function |
Major transport protein for glucocorticoids and progestins in the blood of almost all vertebrate species.
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| BioChemical Class |
Serpin protein
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| UniProt ID | ||||||
| Sequence |
MPLLLYTCLLWLPTSGLWTVQAMDPNAAYVNMSNHHRGLASANVDFAFSLYKHLVALSPK
KNIFISPVSISMALAMLSLGTCGHTRAQLLQGLGFNLTERSETEIHQGFQHLHQLFAKSD TSLEMTMGNALFLDGSLELLESFSADIKHYYESEVLAMNFQDWATASRQINSYVKNKTQG KIVDLFSGLDSPAILVLVNYIFFKGTWTQPFDLASTREENFYVDETTVVKVPMMLQSSTI SYLHDSELPCQLVQMNYVGNGTVFFILPDKGKMNTVIAALSRDTINRWSAGLTSSQVDLY IPKVTISGVYDLGDVLEEMGIADLFTNQANFSRITQDAQLKSSKVVHKAVLQLNEEGVDT AGSTGVTLNLTSKPIILRFNQPFIIMIFDHFTWSSLFLARVMNPV Click to Show/Hide
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| 3D Structure | Click to Show 3D Structure of This Target | PDB | ||||
| HIT2.0 ID | T10OYK | |||||
| Drugs and Modes of Action | Top | |||||
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| Approved Drug(s) | [+] 3 Approved Drugs | + | ||||
| 1 | Alclometasone | Drug Info | Approved | Inflammation | [2] | |
| 2 | Ciclesonide | Drug Info | Approved | Obstructive airway disease | [3], [4], [5], [6] | |
| 3 | Paramethasone | Drug Info | Approved | Inflammation | [7] | |
| Clinical Trial Drug(s) | [+] 1 Clinical Trial Drugs | + | ||||
| 1 | I-vation | Drug Info | Phase 2 | Diabetic retinopathy | [8] | |
| Mode of Action | [+] 2 Modes of Action | + | ||||
| Binder | [+] 3 Binder drugs | + | ||||
| 1 | Alclometasone | Drug Info | [1] | |||
| 2 | Ciclesonide | Drug Info | [9], [10] | |||
| 3 | Paramethasone | Drug Info | [9], [10] | |||
| Modulator | [+] 1 Modulator drugs | + | ||||
| 1 | I-vation | Drug Info | [11] | |||
| Cell-based Target Expression Variations | Top | |||||
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| Cell-based Target Expression Variations | ||||||
| Drug Binding Sites of Target | Top | |||||
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| Ligand Name: Hydrocortisone | Ligand Info | |||||
| Structure Description | Crystal structure of the reactive loop cleaved Corticosteroid Binding Globulin complexed with Cortisol | PDB:2VDY | ||||
| Method | X-ray diffraction | Resolution | 2.30 Å | Mutation | No | [12] |
| PDB Sequence |
GLASANVDFA
25 FSLYKHLVAL35 SPKKNIFISP45 VSISMALAML55 SLGTCGHTRA65 QLLQGLGFNL 75 SETEIHQGFQ88 HLHQLFAKSD98 TSLEMTMGNA108 LFLDGSLELL118 ESFSADIKHY 128 YESEVLAMNF138 QDWATASRQI148 NSYVKNKTQG158 KIVDLFDSPA171 ILVLVNYIFF 181 KGTWTQPFDL191 ASTREENFYV201 DETTVVKVPM211 MLQSSTISYL221 HDSELPCQLV 231 QMNYVGNGTV241 FFILPDKGKM251 NTVIAALSRD261 TINRWSAGLT271 SSQVDLYIPK 281 VTISGVYDLG291 DVLEEMGIAD301 LFTTQANFSR311 ITQDAQLKSS321 KVVHKAVLQL 331 NEEGTEAAGA341 MFLEAIPRKP352 IILRFNQPFI362 IMIFDHFTWS372 SLFLARVMNP 382 V
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| Click to View More Binding Site Information of This Target and Ligand Pair | ||||||
| Ligand Name: Progesterone | Ligand Info | |||||
| Structure Description | Crystal structure of cleaved corticosteroid-binding globulin in complex with progesterone | PDB:4BB2 | ||||
| Method | X-ray diffraction | Resolution | 2.48 Å | Mutation | Yes | [13] |
| PDB Sequence |
> Chain A
HHRGLASANV 22 DFAFSLYKHL32 VALSPKKNIF42 ISPVSISMAL52 AMLSLGTCGH62 TRAQLLQGLG 72 FNLTERSETE82 IHQGFQHLHQ92 LFALEMTMGN107 ALFLDGSLEL117 LESFSADIAH 127 YYESEVLAMN137 FQDWATASRQ147 INSYVKNKTQ157 GKIVDLFSGL167 DSPAILVLVN 177 YIFFKGTWTQ187 PFDLASTREE197 NFYVDETTVV207 KVPMMLQSST217 ISYLHDSELP 227 CQLVQMNYVG237 NGTVFFILPD247 KGKMNTVIAA257 LSRDTINRWS267 AGLTSSQVDL 277 YIPKVTISGV287 YDLGDVLEEM297 GIADLFTNQA307 NFSRITQDAQ317 LKSSKVVHKA 327 VLQLNEEGVD337 TAGSTGVTLN347 LT> Chain B KPIILRFNQP 360 FIIMIFDHFT370 WSSLFLARVM380 NPV
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| Click to View More Binding Site Information of This Target with Different Ligands | ||||||
| Different Human System Profiles of Target | Top |
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Human Similarity Proteins
of target is determined by comparing the sequence similarity of all human proteins with the target based on BLAST. The similarity proteins for a target are defined as the proteins with E-value < 0.005 and outside the protein families of the target.
A target that has fewer human similarity proteins outside its family is commonly regarded to possess a greater capacity to avoid undesired interactions and thus increase the possibility of finding successful drugs
(Brief Bioinform, 21: 649-662, 2020).
Human Tissue Distribution
of target is determined from a proteomics study that quantified more than 12,000 genes across 32 normal human tissues. Tissue Specificity (TS) score was used to define the enrichment of target across tissues.
The distribution of targets among different tissues or organs need to be taken into consideration when assessing the target druggability, as it is generally accepted that the wider the target distribution, the greater the concern over potential adverse effects
(Nat Rev Drug Discov, 20: 64-81, 2021).
Biological Network Descriptors
of target is determined based on a human protein-protein interactions (PPI) network consisting of 9,309 proteins and 52,713 PPIs, which were with a high confidence score of ≥ 0.95 collected from STRING database.
The network properties of targets based on protein-protein interactions (PPIs) have been widely adopted for the assessment of target’s druggability. Proteins with high node degree tend to have a high impact on network function through multiple interactions, while proteins with high betweenness centrality are regarded to be central for communication in interaction networks and regulate the flow of signaling information
(Front Pharmacol, 9, 1245, 2018;
Curr Opin Struct Biol. 44:134-142, 2017).
Human Similarity Proteins
Human Tissue Distribution
Biological Network Descriptors
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There is no similarity protein (E value < 0.005) for this target
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Note:
If a protein has TS (tissue specficity) scores at least in one tissue >= 2.5, this protein is called tissue-enriched (including tissue-enriched-but-not-specific and tissue-specific). In the plots, the vertical lines are at thresholds 2.5 and 4.
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| Degree | 1 | Degree centrality | 1.07E-04 | Betweenness centrality | 0.00E+00 |
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| Closeness centrality | 1.78E-01 | Radiality | 1.29E+01 | Clustering coefficient | 0.00E+00 |
| Neighborhood connectivity | 2.20E+01 | Topological coefficient | 1.00E+00 | Eccentricity | 12 |
| Download | Click to Download the Full PPI Network of This Target | ||||
| Chemical Structure based Activity Landscape of Target | Top |
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| Drug Property Profile of Target | Top | |
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| (1) Molecular Weight (mw) based Drug Clustering | (2) Octanol/Water Partition Coefficient (xlogp) based Drug Clustering | |
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| (3) Hydrogen Bond Donor Count (hbonddonor) based Drug Clustering | (4) Hydrogen Bond Acceptor Count (hbondacc) based Drug Clustering | |
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| (5) Rotatable Bond Count (rotbonds) based Drug Clustering | (6) Topological Polar Surface Area (polararea) based Drug Clustering | |
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| "RO5" indicates the cutoff set by lipinski's rule of five; "D123AB" colored in GREEN denotes the no violation of any cutoff in lipinski's rule of five; "D123AB" colored in PURPLE refers to the violation of only one cutoff in lipinski's rule of five; "D123AB" colored in BLACK represents the violation of more than one cutoffs in lipinski's rule of five | ||
| Target Profiles in Patients | Top | |||||
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| Target Expression Profile (TEP) | ||||||
| Target-Related Models and Studies | Top | |||||
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| Target Validation | ||||||
| References | Top | |||||
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| REF 1 | The anti-inflammatory effects of LY178002 and LY256548. Agents Actions. 1989 Jun;27(3-4):300-2. | |||||
| REF 2 | Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77. | |||||
| REF 3 | URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7469). | |||||
| REF 4 | 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101. | |||||
| REF 5 | Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015 | |||||
| REF 6 | Emerging drugs for asthma. Expert Opin Emerg Drugs. 2008 Dec;13(4):643-53. | |||||
| REF 7 | FDA Approved Drug Products from FDA Official Website. 2009. Application Number: (NDA) 012772. | |||||
| REF 8 | Drug delivery implants in the treatment of vitreous inflammation. Mediators Inflamm. 2013;2013:780634. | |||||
| REF 9 | Novel human corticosteroid-binding globulin variant with low cortisol-binding affinity. J Clin Endocrinol Metab. 2000 Jan;85(1):361-7. | |||||
| REF 10 | A Leu----His substitution at residue 93 in human corticosteroid binding globulin results in reduced affinity for cortisol. J Steroid Biochem Mol Biol. 1992 Aug;42(7):671-6. | |||||
| REF 11 | Cortisol binding in rat skeletal muscle. J Biol Chem. 1975 Feb 25;250(4):1207-11. | |||||
| REF 12 | The S-to-R transition of corticosteroid-binding globulin and the mechanism of hormone release. J Mol Biol. 2008 Jun 27;380(1):244-51. | |||||
| REF 13 | Corticosteroid-binding globulin: structure-function implications from species differences. PLoS One. 2012;7(12):e52759. | |||||
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